Neuropeptide Y antagonistic properties of D-myo-inositol-1.2.6-trisphosphate in guinea pig basilar arteries.
The antagonistic properties on neuropeptide Y (NPY)-induced contraction of the guinea pig basilar artery of D-myo-inositol-1.2.6-triphosphate (PP56) has been examined using a sensitive in vitro system. It was observed that PP56 did not per se cause contraction or relaxation of precontracted vessel segments. However, it was found to be a non-competitive antagonist of NPY-induced contraction. This effect was observed in the concentration range 10(-8)-10(-6) M PP56. A slight potentiation of endothelin I-induced contraction was seen at high concentrations (10(-3) M). In contrast there was no modulation of the contractile effects elicited by bradykinin, noradrenaline, 5-hydroxytryptamine (5-HT) or prostaglandin F2 alpha (PGF2 alpha) apart from a slight reduction in maximum effect at 10(-4) M and 10(-3) M PP56. PP56 was observed to possess antihistaminic and anticholinergic properties in the concentration range 10(-5) M-10(-3) M. The relaxant effects of vasoactive intestinal peptide, calcitonin gene-related peptide, neurokinin A and substance P were only modified to a minor extent by PP56 in concentrations of 10(-4) M and 10(-3) M. In conclusion, PP56 appears to be the first non-peptide which potently and rather selectively antagonizes NPY-induced contractions of the guinea pig basilar artery. In high concentrations, PP56 may modify the responses of other agents tested, including histamine and acetylcholine.
Edvinsson
L
L
Department of Experimental Research, Malmö General Hospital, Sweden.
Adamsson
M
M
Jansen
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D015320:Tachykinins; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D015237:Dinoprost; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D001920:Bradykinin; C059368:atrinositol; D009638:Norepinephrine